85000 research outputs found
Sort by
Augmenting Monte Carlo Tree Search for managing service level agreements
No full textMonte Carlo Tree Search (MCTS) is an algorithmic technique utilized in reinforcement learning, a subfield of artificial intelligence, that combines tree-based search and random sampling for decision-making in uncertain environments. Although MCTS has been successfully used for playing complex games such as Chess and Go, without customizing the original algorithm using domain knowledge, it struggles to effectively solve complex supply chain problems. This study proposes several augmenting mechanisms for MCTS, tailored for managing service level agreements. Furthermore, we enhance the proposed solution for products/services where adjusting the base-stock level is feasible. The results demonstrate that even with non-stationary demand, where most optimization methods reach their limits, employing these augmentation mechanisms significantly improves MCTS performance.</p
A new, national voice for people with experience of mental ill health and potential for allyship
No full textCommunity sector ‘peak bodies’ are groups that generally have two main functions: to represent and advocate for their membership. Around the world, similar groups can be called umbrella organisations, federations or intermediary bodies (Cheverton, 2005). These bodies can work to support, empower, educate and achieve systemic change. They can do this by bringing people together, by advocating and consulting on government policy, providing advice to governments and other organisations, by running campaigns, building capability, raising awareness and undertaking research, among other things.</p
Fabrication of Silk Fibroin-Derived Fibrous Scaffold for Biomedical Frontiers
No full textSilk fibroin (SF), a natural protein derived from silkworms, has emerged as a promising biomaterial due to its biocompatibility, biodegradability, degradation rate, and tunable mechanical properties. This review delves into the intrinsic attributes of SF that make it an attractive candidate for scaffold development in tissue engineering and regenerative medicine. The distinctiveness of this comprehensive review resides in its detailed exploration of recent advancements in the fabrication techniques of SF-based fibrous scaffolds, namely electrospinning, freeze-drying, and 3D printing. An in-depth analysis of these fabrication techniques is conducted to illustrate their versatility in customizing essential scaffold characteristics, such as porosity, fiber diameter, and mechanical strength. The article meticulously discusses process parameters, advantages, and challenges of each fabrication technique, highlighting the innovative advancements made in the respective field. Furthermore, the review goes beyond fabrication techniques to provide an overview of the latest biomedical applications and research endeavors utilizing SF-derived scaffolds. From nerve regeneration and wound healing to drug delivery, bone regeneration, and vascular tissue engineering, the diverse applications underscore the versatility of SF in adopting various biomedical challenges. Finally, the article emphasizes the need for standardized characterization techniques, scalable manufacturing processes, and long-term in vivo studies.</p
The Impact of Varying Lactose-to-Maltodextrin Ratios on the Physicochemical and Structural Characteristics of Pasteurized and Concentrated Skim and Whole Milk–Tea Blends
No full textThis study investigates the impact of substituting lactose with maltodextrin in milk-tea formulations to enhance their physicochemical and structural properties. Various lactose-to-maltodextrin ratios (100:0, 90:10, 85:15, 80:20, 75:25) were evaluated in both post-pasteurized and concentrated skim milk-tea (SM-T) and whole milk-tea (WM-T) formulations. Concentration significantly improved the zeta potential, pH, and browning index in both SM-T and WM-T compared to pasteurization. L:M ratios of 90:10 and 75:25 in WM-T and 90:10 and 80:20 in SM-T showed higher phenolic preservation after concentration due to structural changes resulting from the addition of maltodextrin and water removal during prolonged heating. The preservation effect of phenolic components in both WM-T and SM-T is governed by many mechanisms including pH stabilization, zeta potential modulation, protein interactions, complex formation, and encapsulation effects. Therefore, optimizing milk-tea stability and phenolic preservation through L:M ratio adjustments provides a promising approach for enhancing milk-tea properties.</p
Protein subunit vaccines: Promising frontiers against COVID-19
No full textThe emergence of COVID-19 has posed an unprecedented global health crisis, challenging the healthcare systems worldwide. Amidst the rapid development of several vaccine formulations, protein subunit vaccines have emerged as a promising approach. This article provides an in-depth evaluation of the role of protein subunit vaccines in the management of COVID-19. Leveraging viral protein fragments, particularly the spike protein from SARS-CoV-2, these vaccines elicit a targeted immune response without the risk of inducing disease. Notably, the robust safety profile of protein subunit vaccines makes them a compelling candidate in the management of COVID-19. Various innovative approaches, including reverse vaccinology, virus like particles, and recombinant modifications are incorporated to develop protein subunit vaccines. In addition, the utilization of advanced manufacturing techniques facilitates large-scale production, ensuring widespread distribution. Despite these advancements, challenges persist, such as the requirement for cold-chain storage and the necessity for booster doses. This article evaluates the formulation and applications of protein subunit vaccines, providing a comprehensive overview of their clinical development and approvals in the context of COVID-19. By addressing the current status and challenges, this review aims to contribute to the ongoing discourse on optimizing protein subunit vaccines for effective pandemic control.</p
A new era of immune therapeutics for pancreatic cancer: Monoclonal antibodies paving the way
No full textPancreatic cancer, particularly pancreatic ductal adenocarcinoma, remains a devastating disease with a dismal prognosis and limited survival rates. Despite various drug treatments and regimens showing promise in managing the disease, the clinical outcomes have not significantly improved. Immunotherapy however, has become a forefront area in pancreatic cancer treatment. This approach comprises a range of agents, including small molecule drugs, antibodies, combination therapies, and vaccines. In the last 5-8 years, there has been an upsurge of research into the use of monoclonal antibodies to block receptors on cancer or immune cells, revolutionising cancer treatment and management. Several targets have been identified and studied, with the most encouraging noted in relation to checkpoint markers, namely, antibodies targeting anti-programmed cell death 1 (PD-1) and its receptor PD-L1. Herein, we present the clinical developments in immunotherapy in the last 5 years especially those which have been tested in humans against pancreatic cancer.</p
Urgent call for vaccine supply to Africa amid ongoing Mpox clade I outbreak: addressing a public health emergency of international concern
No full textOn August 14, 2024, the World Health Organization (WHO) declared an outbreak of Mpox (formerly Monkeypox) originating in the Democratic Republic of the Congo (DRC) as a Public Health Emergency of International Concern (PHEIC). One day prior, the African Centres for Disease Control and Prevention (Africa CDC) declared this a Public Health Emergency of Continental Security. This is the second time Mpox has been declared as a PHEIC, leading to public confusion, given that the WHO organization declared the end of the first Mpox emergency in May 2023. It was thought that such an ending of the previous Mpox PHEIC was premature. However, the most recent announcement is not connected to the outbreak of 2022–2023, and the responses cannot be identical.</p
Re-emergence of Chandipura virus in India: Urgent need for public health vigilance and proactive management
No full textA recent re-emergence of the Chandipura virus (CHPV) has been documented in Gujarat, India, echoing the outbreak that occurred two decades earlier in Andhra Pradesh, Maharashtra, and Gujarat. As of July 31, 2024, 148 cases of Acute Encephalitis Syndrome (AES) have been reported in India, with 140 cases across 24 districts in Gujarat. The virus has also spread to Madhya Pradesh (n = 4), Rajasthan (n = 3), and Maharashtra (n = 1). Among the 148 AES cases, 51 have been confirmed as CHPV infections, resulting in 59 deaths.</p
Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood–Brain Barrier
No full textThe N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (AT1R), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) the N-terminal amino group cation, (ii) the Asp sidechain anion and (iii) the Arg guanidino cation. Neutralization of any one of these three charged groups results in a substantial reduction (<5%) in bioactivity, implicating a specialized function for this cluster. In contrast, angiotensin A (ARVYIHPF; AngA) has reduced bioactivity at AT1R; however, replacement of Asp in AngII with sarcosine (N-methyl-glycine) not only restores bioactivity but increases the activity of agonist, antagonist, and inverse agonist analogues. A bend produced at the N-terminus by the introduction of the secondary amino acid sarcosine is thought to realign the functional groups that chaperone the C-terminal portion of AngII, allowing transfer of the negative charge originating at the C-terminus to be transferred to the Tyr hydroxyl-forming tyrosinate anion, which is required to activate the receptor and desensitizes the receptor (tachyphylaxis). Peptide (sarilesin) and nonpeptide (sartans) moieties, which are long-acting inverse agonists, appear to desensitize the receptor by a mechanism analogous to tachyphylaxis. Sartans/bisartans were found to bind to alpha adrenergic receptors resulting in structure-dependent desensitization or resensitization. These considerations have provided information on the mechanisms of receptor desensitization/tolerance and insights into possible avenues for treating addiction. In this regard sartans, which appear to cross the blood–brain barrier more readily than bisartans, are the preferred drug candidates.</p
Mpox strikes once more in 2024: Declared again as a public health emergency of international concern
No full textThe Africa Centres for Disease Control and Prevention (Africa CDC) declared the ongoing Monkeypox (Mpox) outbreak in the Democratic Republic of Congo (DRC) and surrounding areas a ‘public health emergency of continental security’ on August 13, 2024, and subsequently, the World Health Organization (WHO) announced on August 14, 2024 that it is a ‘public health emergency of international concern (PHEIC)’. This occurred 15 months after the WHO ended the previous Mpox emergency on May 11, 2023, which was thought to have ended prematurely. The cases originated in the DRC, with 30 % of the cases being sex workers, and have now spread to the four bordering nations of Burundi, Rwanda, Kenya, and Uganda.</p